Invariant NKT cells act as an adjuvant to enhance Th2 inflammatory response in an OVA-induced mouse model of asthma.

Invariant NKT cells act as an adjuvant to enhance Th2 inflammatory response in an OVA-induced mouse model of asthma.
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DOI:
10.1371/journal.pone.0119901
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Hu S
Hu S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nie H;Yang Q;Zhang G;Wang A;He Q;Liu M;Li P;Yang J;Huang Y;Ding X;Yu H;Hu S

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不变的自然杀伤T细胞(iNKT细胞)是T淋巴细胞的一个独特的亚群,被认为在过敏性支气管哮喘的发展中发挥重要作用。最近,iNKT细胞被证明在CD 4+和CD 8 + T细胞介导的适应性免疫应答中发挥免疫调节作用。过敏原特异性Th 2炎症反应是哮喘适应性免疫反应的重要组成部分。然而,哮喘中Th 2炎症反应的调节功能尚未得到详细研究。在这项研究中,我们研究了在卵清蛋白(OVA)诱导的小鼠哮喘模型中,iNKT细胞对Th 2炎症反应的调节功能。我们的结果表明,α-半乳糖神经酰胺(α-GalCer)给药激活了iNKT细胞,但不能诱导野生型(WT)小鼠的Th 2炎症反应。在OVA诱导的哮喘模型中,α-GalCer给药和iNKT细胞的过继转移显著增强了Th 2炎症反应,包括肺和支气管肺泡灌洗液(BALF)中炎症细胞浸润增加; BALF和脾细胞培养上清液中IL-4、IL-5和IL-13水平升高;以及OVA特异性IgE和IgG 1血清水平升高。此外,与WT小鼠相比,在用OVA免疫和攻击的CD 1d-/-小鼠中,Th 2炎症应答降低,但未完全消除。这些结果表明,iNKT细胞可作为佐剂,以增强在OVA诱导的小鼠哮喘模型中的Th 2炎症反应。
Invariant natural killer T cells (iNKT cells) are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4+ and CD8+ T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail. In this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA)-induced murine model of asthma. Our results demonstrate that α-Galactosylceramide (α-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice. In the OVA-induced asthma model, α-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF); increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice. These results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma.
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影响因子: --
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